Enhancement of basic fibroblast growth factor-stimulated VEGF synthesis by Wnt3a in osteoblasts
Enhancement of basic fibroblast growth factor-stimulated VEGF synthesis by Wnt3a in osteoblasts
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DOI：
10.3892/ijmm.2011.644
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发表时间：
2011-06-01
影响因子：
5.4
通讯作者：
Kozawa, Osamu
中科院分区：
文献类型：
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作者：
Tokuda, Haruhiko;Adachi, Seiji;Kozawa, Osamu
目前认为Writ信号通路调节骨量。我们以前曾报道，碱性成纤维细胞生长因子（FGF-2）刺激血管内皮生长因子（VEGF）的合成，至少部分通过p44/p42丝裂原活化蛋白（MAP）激酶和应激活化蛋白激酶（SAPK）/c-Jun N-末端激酶（JNK）在成骨细胞样MC 3 T3-El细胞。在本研究中，我们研究了Wnt 3a对MC 3 T3-E1细胞中FGF-2刺激的VEGF合成的影响。Writ 3a在1 - 30 ng/ml范围内以剂量依赖性方式显著增强FGF-2刺激的VEGF释放。氯化锂和SB 216763，糖原合成酶激酶3 β（GSK 3 β）的抑制剂，增强了FGF-2刺激的VEGF释放。Wnt 3a不影响FGF-2诱导的p44/p42 MAP激酶、SAPK/JNK、Akt、p38 MAP激酶或p70 S6激酶的磷酸化。Wnt 3a和SB 216763增加FGF-2诱导的VEGF mRNA表达水平。这些结果有力地表明，Wnt 3a通过激活成骨细胞中的经典Wnt/β-连环蛋白途径来增强FGF-2刺激的VEGF合成。
It is currently recognized that the Writ signaling pathway regulates bone mass. We have previously reported that the basic fibroblast growth factor (FGF-2) stimulates the synthesis of the vascular endothelial growth factor (VEGF) at least in part via the p44/p42 mitogen-activated protein (MAP) kinase and the stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) in osteoblast-like MC3T3-El cells. In the present study, we investigated the effect of Wnt3a on FGF-2-stimulated VEGF synthesis in MC3T3-E1 cells. Writ 3a significantly augmented the FGF-2-stimulated VEGF release in a dose-dependent manner in the range between 1 and 30 ng/ml. Lithium chloride and SB216763, inhibitors of glycogen synthase kinase 3 beta (GSK3 beta), enhanced the FGF-2-stimulated VEGF release. Wnt3a did not affect the phosphorylation of the p44/p42 MAP kinase, SAPK/JNK, Akt, p38 MAP kinase or the p70 S6 kinase induced by FGF-2. Wnt3a and SB216763 increased the levels of VEGF mRNA expression induced by FGF-2. These results strongly suggest that Wnt3a enhances VEGF synthesis stimulated by FGF-2 via activation of the canonical Wnt/beta-catenin pathway in osteoblasts.